Stoker Thomas B, Barker Roger A
John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Cambridge, CB2 0PY, UK.
Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge.
Regen Med. 2016 Dec;11(8):777-786. doi: 10.2217/rme-2016-0102. Epub 2016 Nov 25.
Over the past three decades, significant progress has been made in the development of potential regenerative cell-based therapies for neurodegenerative disease, with most success being seen in Parkinson's disease. Cell-based therapies face many challenges including ethical considerations, potential for immune-mediated rejection with allogeneic and xenogeneic tissue, pathological spread of protein-related disease into the grafted tissue as well as the risk of graft overgrowth and tumorigenesis in stem cell-derived transplants. Preclinical trials have looked at many tissue types of which the most successful to date have been those using fetal ventral mesencephalon grafts, which led to clinical trials, which have shown that in some cases they can work very well. With important proof-of-concept derived from these studies, there is now much interest in how dopaminergic neurons derived from stem cell sources could be used to develop cell-based therapies suitable for clinical use, with clinical trials poised to enter the clinic in the next couple of years.
在过去三十年里,基于细胞的潜在神经退行性疾病再生疗法取得了重大进展,其中帕金森病方面取得的成功最为显著。基于细胞的疗法面临诸多挑战,包括伦理考量、同种异体和异种组织免疫介导排斥的可能性、蛋白质相关疾病向移植组织的病理扩散,以及干细胞衍生移植中移植组织过度生长和肿瘤发生的风险。临床前试验研究了多种组织类型,迄今为止最成功的是使用胎儿腹侧中脑移植,这引发了临床试验,试验表明在某些情况下效果非常好。鉴于这些研究提供了重要的概念验证,目前人们对如何利用干细胞来源的多巴胺能神经元来开发适用于临床的基于细胞的疗法兴趣浓厚,未来几年临床试验有望进入临床阶段。